Monitoring Asthma And Other Respiratory Disorders With Calibrated Photoplethysmography Devices And Methods Of Using The Same

ABSTRACT

Provided according to embodiments of the invention are methods of monitoring air obstruction in an individual that include obtaining at least one calibration photoplethysmography (PPG) signal stream from the individual while the individual spontaneously breathes through at least one resistor having a known resistance; using a processing device to determine changes in the at least one calibration PPG signal stream in response to an increase in resistance to the individual&#39;s breathing; obtaining a monitoring PPG signal stream from the individual during spontaneous breathing; and using the monitored PPG signal stream to determine a calibrated resistance value, and using the calibrated resistance value to determine a level of obstruction of the individual&#39;s breathing. Related devices are also provided herein.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.11/334,114, filed on Jul. 17, 2014 and issued as U.S. Pat. No.9,370,635, which is a continuation of U.S. application Ser. No.11/909,004, filed on Apr. 25, 2006 and issued as U.S. Pat. No.8,801,620, which is a U.S. National Phase application of InternationalApplication No. PCT/US06/15763, filed Apr. 25, 2006, which is acontinuation in part of U.S. application Ser. No. 11/122,278, filed Apr.25, 2005, and issued as U.S. Pat. No. 7,785,262. Each of theseapplications is incorporated by reference herein in their entirety.

BACKGROUND

A wide range of respiratory disorders are characterized by periods ofremission interspersed with periods of exacerbation. This group ofdisorders is known to have a reversible component to the diseaseprocesses which can be treated with a wide range of medications andancillary therapies. These disorders range from obstruction of the upperairway, such as with seasonal allergy which can temporarily result inpartial or complete blockage of the nasopharynx to certain types ofsleep apnea which result in temporary partial or complete obstruction ofthe posterior pharynx during phases of the sleep cycle, to disorders ofthe trachea and bronchi (tracheomalacia, tracheal polyps and warts, andbronchitis) and particularly to disorders of the lower airways, such asasthma, cystic fibrosis and chronic Obstructive pulmonary disease (COPD)which are characterized by inflammation and reversiblebronchoconstriction. Exacerbations can run the spectrum from mild tolife threatening and in many instances it is difficult for the patient,or in the case of a child, for the parent, to gauge the severity of therelapse.

Typically, physical examination by a physician and/or ancillary testssuch as spirometry, pulse oximetry and arterial blood gases are used togauge the degree of exacerbation. For some diseases, which occurperiodically or during sleep, it is necessary to admit the patient tothe hospital for formal and extensive testing to diagnose the etiologyand severity of the disease. Patients with these disorders frequentemergency departments and physician's offices for diagnosis andtreatment as it is difficult for them to gauge when a visit isappropriate and thus they consume a considerable amount of healthcareresources, often unnecessarily. Sleep apnea is the temporary absence orcessation of breathing during sleep, thereby causing oxygen to ceaseentering the body leading to hypoxemia (lack of oxygen in the blood) andoften, for carbon dioxide (CO₂) to accumulate in the blood(hypercarbia). In general, when there is lack of oxygen delivery due tosleep apnea, the oxygen saturation (SpO₂), i.e., an amount of oxygen inthe blood, decreases to an abnormally low level and CO₂ can increase toabnormally high levels.

Sleep fragmentation during sleep apnea causes excessive daytimesleepiness (EDS) and hypoxemia during sleep. Chronic declines in oxygensaturation and increased CO₂ may cause high blood pressure, arrhythmia,or other serious cardiovascular abnormalities. Occasionally, a declinein oxygen saturation and/or rise in CO₂ may even have fatal results bycausing a heart attack while a person is sleeping or increasing thelikelihood while they are awake. It is reported that about 20 percent ofthe adult population of the United States suffers from snoring, andabout 50 percent of those people that snore suffer from sleep apnea.

Children with sleep apnea display unique symptoms such as decreasedattention span, erratic behavior, EDS, irregular sleep, rib cageretraction, and flaring of the ribs. Such children may do poorly in anacademic setting and, in the most serious cases, may suffer from mentalor psychological disorders. For infants or babies, sleep apnea may causesudden death during sleep. Sleep apnea is typically classified intothree main types: obstructive, central, and mixed. Obstructive sleepapnea is the most common form of sleep apnea and is characterized by arepeated closing of the upper airway on inspiration. Central sleep apneaoccurs when the brain fails to send adequate signals to the diaphragmand lungs during sleep, thereby resulting in decreased respiration.Mixed sleep apnea is a combination of obstructive sleep apnea andcentral sleep apnea. Regardless of the type of sleep apnea, it resultsin a decrease in SpO₂ and often retention of CO₂. Interestingly,children may manifest only CO₂ retention, without the classical findingof decreased SpO₂. Thus, one of the major tools for diagnosing sleepapnea, pulse oximetry for measuring SpO², may be of little value indiagnosing sleep apnea in children. A breathing disorder is clinicallyclassified as sleep apnea when a cessation of breathing lasting for tenor more seconds occurs at least five times an hour or at least thirtytimes in a seven-hour period. Snoring is a sound made when a soft palateof the upper airway vibrates, and thus, is often a direct indicator ofsleep apnea.

Polysomnography (PSG) is a test during which sleep architecture andfunction and behavioral events during sleep are objectively measured andrecorded. See U.S. Patent Publication No. 2002/0165462. Morespecifically, a number of physiological variables, such as brain waves,eye movement, chin electromyogram, leg electromyogram,electrocardiogram, snoring, blood pressure, respiration, and arterialoxygen saturation, are measured extensively. At the same time,behavioral abnormalities during sleep are recorded with video taperecorders. Trained technicians and sleep specialists read the record toobtain comprehensive results about the severity of snoring, whetherarrhythmia occurs, whether blood pressure increases, whether otherproblems are caused during sleep, and at what points the record differsfrom normal sleep patterns.

Full polysomnography is, however, quite labor intensive, requiresconsiderable instrumentation and is therefore expensive to conduct. As aresult, many sleep laboratories have found it difficult to keep up withthe demand for this test, and long waiting lists have become the norm.Further, many patients find it difficult to sleep adequately whenmonitored and in strange surroundings. Given that obstructive sleepapnea (OSA) is quite prevalent, leads to serious complications and thattreatment options exist, it is important that individuals suffering fromthe disease are identified.

A conventional full overnight PSG includes recording of the followingsignals: electroencephalogram (EEG), submental electromyogram (EMG),electrooculogram (EOG), respiratory airflow (oronasal flow monitors),respiratory effort (respiratory plethysmography), oxygen saturation(oximetry), electrocardiography (ECG), snoring sounds, and bodyposition, These signals are considered the “gold standard” for thediagnosis of sleep disorders in that they offer a relatively completecollection of parameters from which respiratory events may be identifiedand SA may be reliably diagnosed. The RR interval, is derived from theECG and provides the heart rate and arrhythmia recognition. Bodyposition is normally classified as: right side, left side, supine,prone, or up (or sitting erect). Typically, the microphone and the bodyposition sensor are taped over the pharynx. Each signal provides someinformation to assist in the visual observation and recognition ofrespiratory events.

Collapse of the upper airway is conventionally defined in PSG studies aswhen the amplitude of the respiratory airflow decreases by at least 50%,snoring sounds either crescendo or cease, and oxygen desaturationoccurs. An obstruction event is confirmed (i.e., desaturation not anartifact) by the recognition of an arousal (i.e., the person awakens tobreathe), typically identified by an increase in the frequency of theEEG, an increase in heart rate, or change in snoring pattern. Theremaining signals assist in determining specific types of obstructionevents. For example, the EEG and EOG signals are used to determine if anobstruction event occurred in non-rapid eye movement (NREM) or rapid eyemovement (REM) sleep. The position sensor is used to determine if anairway collapse occurs only or mostly in just one position (typicallysupine).

A reduction or absence of airflow at the airway opening definessleep-disordered breathing. Absent airflow for 10 seconds in an adult isdefined as apnea, and airflow reduced below a certain amount ishypopnea. Ideally one would measure actual flow with a pneumotachometerof some sort, but in clinical practice this is impractical, and devicesthat are comfortable and easy to use are substituted. The most widelyused are thermistors placed in front of the nose and mouth that detectheating (due to expired gas) and cooling (due to inspired air) of athermally sensitive resistor. They provide recordings of changes inairflow, but as typically employed are not quantitative instruments.Currently available thermistors are sensitive, but frequentlyoverestimate flow. Also, if they touch the skin, they cease being flowsensors. Measurement of expired CO₂ partial pressure is used in somelaboratories to detect expiration, but it is not a quantitative measureof flow.

In sum, the inventors have realized that conventional apparatuses andmethods for diagnosing sleep apnea and other respiratory disorders haveseveral disadvantages including being difficult to implement, beingunable to detect all three types of sleep apnea, being unable to provideaccurate and reliable results, and causing discomfort in a subject beingmonitored.

SUMMARY

Therefore, the inventors have discovered that there is a substantialneed in the art for a device and method that will allow patients andtheir healthcare providers to rapidly and accurately diagnose airobstruction brought about by respiratory disorders and quantifyexacerbations so appropriate treatment, if necessary, can be startedexpeditiously. Further, the inventors have realized that there is aparticular need for a small portable device that can be used by thepatient in the home or workplace to determine when an exacerbation hasoccur and whether they are in need of immediate medical attention.

Sleep apnea represents one such disorder in which the instant device andmethod could be used. In one embodiment it would allow for screening ofsubjects in the home as the number of hospital beds allocated for sleepstudies is far exceeded by the number of patients that require studies.Subjects that are shown to have characteristics of sleep apnea on homescreening could then be scheduled for formal studies, but moreimportantly, subjects who do not have charactetistic findings could beexcluded, thus reducing the number of negative studies performed inhospitals. Further, the device and method could be used during hospitalstudies to diagnose patients, such as children, who have types of sleepapnea that are difficult to diagnose with conventional equipment and whooften do not tolerate many of the monitoring devices. Sleep apnea willbe used as an example of how the instant device and method can beapplied, but it is applicable to a wide range of respiratory diseases.

According to one aspect, the subject invention pertains to a method ofdiagnosing air obstruction events in a patient, said method comprisingsecuring a pulse oximeter probe to a central source site of said patientwherein said probe is configured to generate a signal stream indicativeof blood flow at said central source site; processing said signal streamreceived from said probe to obtain a separate pulsatile arterialcomponent signal and venous impedance component signal; and evaluatingsaid pulsatile arterial component signal, or venous impedance componentsignal, or both, to determine the occurrence and degree of an airobstruction event. The method allows for the comfortable andnon-invasive monitoring of respiratory rate and degree of airwayobstruction in the context of sleep studies for diagnosing respiratoryrelated sleep disorders, as well as for a large number of otherrespiratory conditions characterized by diminished airflow and increasedinspiratory and/or expiratory respiratory effort to breath. According toanother aspect, the subject invention pertains to a method of monitoringrespiration and/or degree of airway obstruction of a patient. The methodsupplants the need for uncomfortable and potentially unreliable gas flowsensors placed in or proximal a patient's mouth or nose.

Another aspect of the subject invention pertains to a method ofmonitoring respiration in a patient, the method comprising securing apulse oximeter probe to a central source site of the patient wherein theprobe is configured to generate a plethysmography signal stream from thecentral source site; processing the signal stream received from theprobe to obtain a separate arterial component signal and venousimpedance component signal; and evaluating the arterial componentsignal, or venous impedance component signal, or both, to determinerespiratory rate, occurrence of an inspiratory event, expiratory event,air restriction or air obstruction, or a combination thereof.

Another aspect of the subject invention pertains to a system formonitoring respiration and/or airway obstruction of a patient. Thesystem comprises one or more pulse oximeter probes configured forsecurement to a central source site of a patient and to generate signalsindicative of blood flow at said central source site. The system alsocomprises a computer communicatingly connected to one or more pulseoximeter probes. The computer comprises a processing module, a firstcomputer-readable program code module for causing the computer toprocess signals of the one or more pulse oximeter probes to obtain avenous impedance component signal isolated from a pulsatile arterialcomponent signal, and a second computer-readable program code module forcausing the computer to analyze the venous impedance component signal todetermine an inspiratory event, expiratory event or an air obstructionevent, or a combination thereof.

In yet a further aspect, the subject invention pertains to a method ofdiagnosing a respiratory condition comprising collecting a first datasetof plethysmography signal information from a patient generated duringrespiration at one or more predetermined resistances; collecting asecond dataset of plethysmography signal information from the patientduring a period where said patient is suspected of experiencing airrestriction or air obstruction; comparing the second dataset to saidfirst dataset; and diagnosing a respiratory condition based on thecomparison. Another aspect of the subject invention is a method todetermine the magnitude of change in the pulsatile arterial and venousimpedance components of the photophotoplethysmograph on a patient whiletheir respiratory status is normal or near normal by having the patientbreath through a series of graded resistors and to store and use thisinformation to determine the degree and seriousness of airwayobstruction during an exacerbation.

These and other advantageous aspects of the invention will be describedin further detail herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B represent graphs demonstrating the effects of airwaymaneuvers on photoplethysmography when obtained from a central site.FIG. 1A shows the effect of airway maneuvers on an AC component (orarterial component) of a photoplethysmography signal; and FIG. 1B showsthe effect of maneuvers on the DC component (or venous impedancecomponent).

FIGS. 2A and 2B represent graphs showing the effects of breathingthrough a series of resistors on the photoplethysmography signalobtained from a central site; FIG. 2A shows the arterial component andFIG. 2B shows the venous impedance component.

FIG. 3 shows a schematic of a system for monitoring respiration orconducting sleep studies on a patient that employs plethysmographysignals obtained from the patient.

FIG. 4 shows a schematic of a system for monitoring respiration orconducting sleep studies on a patient that employs plethysmographysignals obtained from the patient.

FIG. 5 shows a diagram representing a method for conducting a study todetermine occurrence of abnormal respiratory events.

FIG. 6 shows a diagram representing a method for conducting a study todetermine occurrence and magnitude of abnormal respiratory events.

FIG. 7 shows a diagram representing a method for conducting a study todetermine abnormal respiratory events.

FIG. 8 shows a diagram representing a method for monitoring respirationof a patient.

FIGS. 9A-9C represent a graph containing plethysmography, PAC and VICreadings from a patient undergoing mechanical ventilation at differentlevels of PEEP. FIG. 9A shows the raw plethysmography signals taken atthe nasal alar and at the finger. FIG. 9B shows the PAC of the nasalalar plethysmography signal shown in FIG. 9A. FIG. 9C shows the VIC ofthe nasal alar plethysmography signal shown in FIG. 9A.

FIGS. 10A-10C represent a graph containing plethysmography, PAC and VICreadings from a patient undergoing mechanical ventilation at differentlevels of PEEP. FIG. 10A shows the raw plethysmography signals taken atthe nasal alar and at the finger. FIG. 10B shows the PAC of the nasalalar plethysmography signal shown in FIG. 10A. FIG. 10C shows the VIC ofthe nasal alar plethysmography signal shown in FIG. 10A.

FIGS. 11A-11C represent a graph containing plethysmography, PAC and VICreadings from a patient undergoing mechanical ventilation at differentlevels of PEEP. FIG. 11A shows the raw plethysmography signals taken atthe nasal alar and at the finger. FIG. 11B shows the PAC of the nasalalar plethysmography signal shown in FIG. 11A. FIG. 11C shows the VIC ofthe nasal alar plethysmography signal shown in FIG. 11A.

DETAILED DESCRIPTION

According to one embodiment, the subject invention is directed to amethod of diagnosing whether a patient is likely to experience airwayobstruction during sleep through the use of photoplethysmography. To theinventors knowledge, no one has previously thought of usingphotoplethysmography for such purpose or for the diagnosis of airwayobstruction as manifest by an exacerbation of other respiratorydiseases. Traditionally, a plethysmography signal stream is typicallyobtained from a peripheral site such as the finger, or other extremity,which is usually damped and difficult to process and therefore tointerpret. The inventors have discovered that obtaining thephotoplethysmograph from a central site eliminates much of thebackground noise and poor signal to noise ratio found in theplethysmograph from a peripheral site, and it is the obtention of this“less noisy” signal that eventually led to the realization thatinformation such as respiration rate, pulsatile arterial blood flow,degree of airway obstruction and venous impedance can be extrapolated.

Typically, photoplethysmography is conducted using one pulse oximeterprobe. The raw signal stream obtained from a pulse oximeter probe isrelated to the amount of light from the LED that hits the photodetectorof the pulse oximeter probe. The magnitude of the signal from thephotodetector is inversely proportional to the amount of absorption ofthe light between the LED and the photodetector (greater absorptionresults in less light exciting the photodetector). The absorbed light isdue to multiple factors, including absorption due to tissue, absorptiondue to venous blood, absorption due to arterial blood, and absorptiondue to the pulsation of arterial blood with each heart beat. Typically,the raw signal from the photodetector is processed (e.g. removal ofartifacts and autogain of the signal) in order to obtain an arterialoxygen saturation value and the plethysmograph is largely ignored.Significant confusion and overlap exists in the terminology used indescribing various aspects of pulse oximetry. On one hand, the terms ACcomponent and DC component are used to describe the anatomicalstructures responsible for the photoplethysmograph (ACcomponent—pulsatile blood flow in arteries, arterioles and possiblycapillaries) and the components responsible for attenuating the signal(DC component—venous blood, tissue, bone, etc.) The terms are also usedto describe the phasic rapid pulsatile flow in the arteries andarterioles as seen in the plethysmography (AC component) as contrastedwith slower (DC) components of the plethysmograph.

As the AC component and DC component can have different meanings in theart, the AC component will also be referred to herein as the “pulsatilearterial” component (PAC), and the DC component will also be referred toherein as the “venous impedance” component (VIC). Thus, we use the termAC component to describe a component of a processed plethysmographicsignal that represents the pulsatile blood flow that is present in thevascular bed being monitored. The DC component, as used herein, is aphasic slower frequency signal that represents the venous impedance ofblood in the vascular bed being monitored and is influenced byvariations in intrathoracic pressure and venous blood volume. Thepulsatile arterial signal has been typically called the plethysmographand the VIC overlooked, although it is present in the signal and can beisolated as described later. A further distinction must be made betweenthe term “DC component” and the term “DC offset”. The popular usage ofthe term DC component has been described above. The term “DC offset”refers to the amount that the plethysmographic signal is shifted from abaseline that would be present if no light excited the photodiode. Theplethysmographic signal is small relative to the magnitude of the DCoffset, and “rides” on the DC offset signal. The DC offset varies withthe intensity of the LEDS and the amount of light absorbed by thetissues. Thus, if the light path through tissue remains constant, the DCoffset increases with increasing LED power, and decreased with less LEDpower. Alternatively, the DC offset increases as the path alight throughthe tissues decreases and decreases as the path of light through thetissues increases. Manufacturers usually have circuits built into thepulse oximeter to keep the LED power in a range in which the DC offsetwill be an adequate signal to discern the photoplethysmograph, but lessthan that which will oversaturate the photodiode.

According to one signal processing method embodiment of the subjectinvention, the effects of the individual heart beats in theplethysmograph are separated out from the other information, which isfundamentally a different goal than conventional processing, which isbasically to obtain an adequate arterial component and discarding thevenous impedance component. Standard practice is to implement a DCremoval technique that involves removing the venous impedance componentby a low pass filter This technique, however, does not sufficientlyseparate all of the data from the two sources of information. Thesubject processing method obtains a higher fidelity signal, which iscritical when dealing with precise measurements of variables fordetermining, for example, respiratory events in a patient.

In a specific embodiment, the high fidelity pulsatile arterial componentand the venous impedance component of the plethysmography signal(previously ignored by those in the art) are achieved by unique signalprocessing, comprising:

-   -   1) discretely selecting the peaks and troughs of the signal        (improved noise/artifact rejection can be achieved by looking        for peaks and troughs that exist at the expected heart rate,        estimated by Fourier or autocorrelation analysis, or from past        good data)    -   2) finding the midpoints (or minimum values) between peaks and        troughs    -   3) extracting the venous impedance component as the interpolated        (and possibly smoothed or splined) line that connects these        midpoints (or minimum values)    -   4) extracting the pulsatile arterial component as the raw signal        subtracted from the venous impedance component.

This processing is preferably implemented from signals obtained from acentral source site, but it could be applied to signals obtained fromother sites so long as the fidelity of the signal is sufficiently highand reliable This technique achieves a nonlinear filter with zero delayand optimally separates the two signals of interest. In view of theteachings herein, those skilled in the art will appreciate that similartechniques for achieving these objectives could also be adapted, and aredifferentiated from the conventional processing of plethysmographysignals due to their goal of optimally separating the two signals ofinterest on a beat-to-beat, zero delay basis (unlike standard linearfiltering, DC removal techniques, and averaging techniques).

The AC and DC components, as described herein, are intended to be thetime varying signals that are related to the beat-to-beat variationscaused by the pulsation and therefore, when recorded over time, the flowof blood in the arteries (the AC component, although different from theAC component described by others), and the slowly varying componentsthat are related to the other physiologic and physical properties of thesignal related to the impedance of the venous vessels and the changes inintrathoracic pressure, the venous (DC) component which differs from the“classical” description of the DC component which is said to includenon-pulsatile arterial blood, pulsatile and non-pulsatile venous bloodand tissue and bone. The amplitude and area under the curve (AUC) of theAC component contains information about the amount of arterial bloodflowing past the detector, in order to correctly interpret thisinformation, the AC and DC components must be separated more rigorouslythan with the algorithms in standard monitors and previously describedin the literature, in particular, the pulsatile arterial componentshould contain only that information that relates to beat-to-beatvariations of the heart The DC component should contain lower frequencyeffects from physiology such as the respiratory effects, blood pooling,venous impedance, etc.) and physical sensor changes (e.g. changes in theorientation of the probe, etc.).

Accordingly, the inventors have discovered and characterized for thefirst time at least three separate components of the plethysmographsignal: (a) blood pulsation signal, (b) time-varying DC signal or venousimpedence signal, and (c) the classical DC component signal which is afunction of the tissue (muscle, bone, etc) at the probe site, and is thebaseline DC component on which the venous impedence signal rides.

Pulse oximeter probes useful in accordance with the teachings hereininclude, but are not limited to, those described in co-pending U.S.application Ser. Nos. 10/176,310; 10/751,308; 10/749,471; and60/600,548, the disclosures of which are all incorporated herein intheir entirety.

As referred to above, the VIC of the photoplethysmograph is an indicatorof venous impedance, while the PAC is a measure of regional blood flow.During forced airway maneuvers, intrathoracic pressure changesdramatically. These pressure changes are transmitted directly to theveins in the head, because there are no anatomical valves in veinsleading to the head. Changes in intrathoracic pressure have directeffects on both the beat to beat pulsatile arterial blood flow (PAC),and the amount of venous blood in the vascular bed being monitored on abreath to breath basis. These effects are present even during quietbreathing, but are far more pronounced with “airway maneuvers” such asthe Valsalva and Mueller maneuvers, and during exacerbation ofrespiratory conditions which increase airway resistance and/or decreaselung compliance. These pronounced changes are often referred to as“pulsus paradoxus” when measured by arterial blood pressure or directarterial blood monitoring. All conditions which affect airway resistance(increase) and lung compliance (decreased) increase the respiratorymuscle work (work of breathing for each breath, or power of breathingfor the amount of work performed in one minute). As the work or power ofbreathing increases, there are wider swings in intrathoracic pressurewhich in turn lead to phasic variations in pulsatile arterial blood flowand venous impedance. Respiratory rate can be easily determined whenmonitoring at “central source sites” and the degree of change in boththe AC and DC components are proportional to the degree of airwayobstruction and/or lung compliance. At a given level of resistance andor compliance, variations in the amplitude and AUC of both componentscan also be an indication of volume status. Thus, a plethora ofinformation on both respiratory and cardiopulmonary mechanics can beascertained from the processed plethysmograph, especially when it isobtained from a “central source site”.

Algorithms to evaluate the PAC and VIC include, but are not limited to,separating the high frequency information in the PAC (heart rate andabove, typically above 0.75 Hz) information, the low frequencyinformation in the VIC (e.g. respiratory rate and changes in blood flow,typically from 0.05 Hz to 0.75 Hz) and the very low frequencyinformation in the DC offset (e.g. changes in pulse oximeter path length(positioning), typically less than 0.05 Hz). Separating these waveformswithout delays or significant averaging is required to optimally extractinformation from the photoplethysmograph (PPG,). The PPG typically hasonly 2-3 heart beats (the major feature of the signal) for each breath(the second largest signal). If significant averaging or delays exist,the secondary signal (VIC) cannot be reliably separated from the primarysignal (PAC). Other methods exist that can be utilized to extract thesesignals. Wavelets allow for finer resolution at low frequencies than themore standard Fourier spectral analysis methods. Adaptive filtering mayalso be used to optimally adjust the cutoff frequency between thebreathing rate and heart rate. If coarse information is all that isrequired, many standard methods can be used to separate the signals,including linear filtering, frequency domain filtering, time domainanalysis such as zero-crossings and moving averages, nonlinearfiltering, modeling such as kalman filtering and ARMA modeling, andother methods known to those skilled in the art.

Quantification of the PAC and VIC changes can include peak or troughcounting, peak-peak timing, peak-trough height, area under the curve,shape of the curves, frequency characteristics of the curves, entropy ofthe curves, changes in the positions of the peaks, troughs, or midpointsfrom heart beat to heart beat or breath to breath. Some of theseparameters may need to be normalized by the LED signal power, DC offset,or the physiology of the probe placement.

The term “central source site” as used herein refers to a site at orabove the patient's neck. Particularly preferred central source sites,include, but are not limited to, a patient's nasal septum, nasal alar,pre-auricular region, post auricular region, tongue, forehead, lip, orcheek, ear canal, or combinations thereof.

The term “obstruction” as used in the context of respiration refers to ablockage of air flow. The blockage may be partial or complete. The term“restriction” as used in the context of respiration is related toobstruction, and in some instances interchangeable with obstruction; andrefers to a restriction of air flow. For example, partial obstruction ofair flow is interchangeable with restriction and complete restriction isinterchangeable with complete obstruction. Unless otherwise indicatedherein, restriction refers to a partial obstruction, i.e., some air isallowed to pass, and obstruction refers to complete blockage of airflow.

The term “processing module” may include a single processing device or aplurality of processing devices. Such a processing device may be amicroprocessor, micro-controller, digital signal processor,microcomputer, central processing unit, field programmable gate array,programmable logic device, state machine, logic circuitry, analogcircuitry, digital circuitry, and/or any device that manipulates signals(analog and/or digital) based on operational instructions. Theprocessing module may have operationally coupled thereto, or integratedtherewith, a memory device. The memory device may be a single memorydevice or a plurality of memory devices. Such a memory device may be aread-only memory, random access memory, volatile memory, non-volatilememory, static memory, dynamic memory, flash memory, and/or any devicethat stores digital information. A computer, as used herein, is a devicethat comprises at least one processing module.

As will be appreciated by one of skill in the art, embodiments of thepresent invention may be embodied as a device, method, or systemcomprising a processing module, and/or computer program productcomprising at least one program code module. Accordingly, the presentinvention may take the form of an entirely hardware embodiment or anembodiment combining software and hardware aspects. Furthermore, thepresent invention may include a computer program product on acomputer-usable storage medium having computer-usable program code meansembodied in the medium. Any suitable computer readable medium may beutilized including hard disks, CD-ROMs, DVDs, optical storage devices,or magnetic storage devices.

The computer-usable or computer-readable medium may be or include, forexample, but not limited to, an electronic, magnetic, optical,electromagnetic, infrared, or semiconductor system, apparatus, device,or propagation medium. More specific examples (a non-exhaustive list) ofthe computer-readable medium would include the following: an electricalconnection having one or more wires, a portable computer diskette, arandom access memory (RAM), a read-only memory (ROM), an erasableprogrammable read-only memory (EPROM or Flash memory), an optical fiber,and a portable compact disc read-only memory (CD-ROM), a CD ROM, a DVD(digital video disk) or other electronic storage medium. Note that thecomputer-usable or computer-readable medium could even be paper oranother suitable medium upon which the program is printed, as theprogram can be electronically captured, via, for instance, opticalscanning of the paper or other medium, then compiled, interpreted orotherwise processed in a suitable manner if necessary, and then storedin a computer memory.

Computer program code for carrying out operations of certain embodimentsof the present invention may be written in an object oriented and/orconventional procedural programming languages including, but not limitedto, Java, Smalltalk, Perl, Python, Ruby, Lisp, PHP, “C”, FORTRAN, orC++. The program code may execute entirely on the user's computer,partly on the user's computer, as a stand-alone software package, partlyon the user's computer and partly on a remote computer or entirely onthe remote computer. In the latter scenario, the remote computer may beconnected to the user's computer through a local area network (LAN) or awide area network (WAN), or the connection may be made to an externalcomputer (for example, through the Internet using an Internet ServiceProvider).

Certain embodiments of the present invention are described herein withreference to flowchart illustrations and/or block diagrams of methods,apparatus (systems) and computer program products according toembodiments of the invention. It will be understood that each block ofthe flowchart illustrations and/or block diagrams, and combinations ofblocks in the flowchart illustrations and/or block diagrams, can beimplemented by computer-readable program code modules. These programcode modules may be provided to a processing module of a general purposecomputer, special purpose computer, embedded processor or otherprogrammable data processing apparatus to produce a machine, such thatthe program code modules, which execute via the processing module of thecomputer or other programmable data processing apparatus, create meansfor implementing the functions specified in the flowchart and/or blockdiagram block or blocks.

These computer program code modules may also be stored in acomputer-readable memory that can direct a computer or otherprogrammable data processing apparatus to function in a particularmanner, such that the program code modules stored in thecomputer-readable memory produce an article of manufacture.

The computer program code modules may also be loaded onto a computer orother programmable data processing apparatus to cause a series ofoperational steps to be performed on the computer or other programmableapparatus to produce a computer implemented process such that theinstructions which execute on the computer or other programmableapparatus provide steps for implementing the functions specified in theflowchart and/or block diagram block or blocks.

During airway maneuvers or with many pulmonary diseases intrathoracicpressure increases above ambient pressure during exhalation (e.g.,asthma, COPD, Valsalva, exhalation through a resistor). Likewise, airwaymaneuvers or pulmonary diseases can cause greater than normal decreasesin intrathoracic pressuring during inspiration (e.g., Mueller maneuver,asthma, COPD, obstructive sleep apnea, inspiration through a resistor).Using the example of an asthmatic patient, between asthmatic episodesbreathing spontaneously, airway resistance is normal or near normal,therefore there should be little phasic change in the PAC, and onlysmall changes in the VIC. Additionally, if the patient breathes at aprescribed flow rate through graded resistors of known sizes, thereshould be phasic changes in the PAC and VIC of the photoplethysmograph.By adding resistance, great excursions in the PAC and VIC are affected.The PAC develops an increasingly apparent “saw tooth” pattern and theVIC will have wider swings above and below baseline, thus increasedamplitude. By calibrating these changes using resistors while a patientis well, these degrees of change can be correlated with each resistor.As such, a patient respiratory profile is created. When the patient issymptomatic, the PAC and VIC changes should reflect the degree ofbronchiolar obstruction/resistance equivalent to that seen whenbreathing through resistors. This can be particularly valuable indetermining the degree and seriousness of obstruction and the responseto therapy. If either a high degree of obstruction is diagnosed, orthere is a poor response to therapy, the patient should present to theEmergency Department (ED). The same measurements can be used in the EDor hospital to follow the course of treatment. Once a profile of the PACand VIC response to resistors is obtained for a patient, the profile canbe stored in a database and used whenever the patient has anexacerbation. Similar profiles can be obtained on patients with a widerange of respiratory diseases, and can be obtained betweenexacerbations, or if the patient is having an exacerbation, the changesin the PAC and VIC can be correlated with measurements made withconventional respiratory monitors, such as a spirometer.

In certain method embodiments, the present invention can monitor anddetect respiratory problems caused by disorders, including but notlimited to, obstruction of the upper airway, such as with seasonalallergy which can temporarily result in partial or complete blockage ofthe nasopharynx to certain types of sleep apnea which result intemporary partial or complete obstruction of the posterior pharynxduring phases of the sleep cycle, to disorders of the trachea andbronchi (tracheomalacia, tracheal polyps and warts, and bronchitis) andparticularly to disorders of the lower airways, such as asthma, cysticfibrosis and chronic obstructive pulmonary disease (COPD) which arecharacterized by inflammation and reversible bronchoconstriction.

During an obstructive event, it is the inventors' belief that eachexhalation will cause less negative or, in some cases, even positiveintrathoracic pressure and each inhalation will cause a more negativeintrathoracic pressure compared to breathing without obstruction. Theinventors have realized that these greater than normal intrathoracicpressure excursions will cause an attenuation of the PAC (less bloodflow per beat) and an increase in the VIC. The more negativeintrathoracic pressure during inhalation will cause an increase in theVIC (more venous return) and a decrease in the PAC. By measuring thesechanges during a known calibration period with known resistors, acomparison of the PAC and VIC changes can be made with the knownresistor changes. Each breath will provide dramatic swings in the PACand VIC. Therefore, one method embodiment for determining airwayocclusion severity includes the following: record data from normal quietbreathing and conscious slow breathing from a series of breaths (e.g, 5,10, 15, 20 etc. breaths), followed by recording photoplethysmographicdata from similar breathing with resistors as described in Example 2below. The data obtained may be put in a table form. The data collectedmay be modulated with appropriate outlier and noise rejection.Optionally, this data may be compared to the calibration data tablescollected on a population of patients to ensure its validity andpossibly classify or cluster the patient with responses from other knownpatients. From the calibration table, a level of occlusion (or anestimated airway resistance) can be determined dynamically by comparingthe changes in PAC and VIC with the recorded data during calibration.Those skilled in the art will appreciate that these values could also beused in a classification scenario where the patient is deemed to havedegrees of occlusion based upon different ranges of resistance (e.g.resistance >40 (units are cmH₂O/L/sec if you are referring toresistance)=near or total occlusion, resistance <40 but >20=partialocclusion, etc.).

In a specific embodiment, a hand-held or otherwise transportablemonitoring device is provided and a patient calibrates the device usinga series of resistors. The device may have different function modes,such as a calibration mode and a monitoring mode to assist in thisprocess. During the calibration mode, the device is calibrated to obtainPAC and VIC component values pertaining to inspiratory and/or expiratoryresistors at increasing levels of resistance. These values are stored inthe device. When it is suspected that the patient is experiencing alevel of obstruction, the patient is monitored with the device in amonitoring mode. During monitoring mode, the PAC and/or VIC values areobserved and compared to those obtained during calibration mode. Thedevice preferably has a readout screen to display information, and ispreferably configured to display the degree of severity of theObstruction event. This device and methodology may be implemented tomonitor the presence and/or severity of air obstruction events fordifferent respiratory conditions. In addition, this methodology willprovide information regarding the type of air obstruction event, i.e.,inspiratory and/or expiratory which will greatly assist in diagnosis ofa person's respiratory problem.

Example 1

FIGS. 1A-1C and 2A-2B demonstrate the ability of photoplethysmography todetect and differentiate different types of airway obstruction. Changesin the PPG are directly related to changes in intrathoracic pressure.Intrathoracic pressure is related to breathing effort which is relatedto the patient's lung dynamics compliance, resistance, chest wallcompliance, etc.), airway characteristics (especially resistance), andbreath characteristics (e.g. flow profile and tidal volume). Duringcomplete airway occlusion, airway pressure and intrathoracic pressureequalize. As such, during complete airway occlusion, a good estimate ofthe intrathoracic pressure can be measured with a simple pressure sensorat the airway. A patient can be asked to breath in and out against aspecial mouthpiece occlusion device that dynamically measures airwaypressure. The airway pressure will reflect intrathoracic pressure andcan be used to calibrate the PPG changes more precisely. Other scenariosthat provide information include an occlusion test where the patientmakes either a maximal inspiratory effort after complete exhalationagainst a dosed glottis (or a plugged piece of tubing) and/or a maximalexpiratory effort against a closed glottis or plugged tubing after amaximal inspiration. These maneuvers are called the Mueller and Valsalvamaneuvers, respectively.

FIGS. 1A and 1B demonstrate the effects of performing Mueller andValsalva maneuvers on the photophotoplethysmograph. Mueller maneuvers,which simulate obstructive sleep apnea (i.e., inspiratoryobstruction/resistance, reproducibly show an increase in the “upswing”of the VIC due to the increase venous return induced by increasednegative intrathoracic pressure. Valsalva maneuvers simulate expiratoryobstruction as seen in asthma and to a lesser extent in obstructivesleep apnea. Valsalva maneuvers result in an increase in the “downswing”of the VIC due to trapping of venous blood in the head secondary to lessnegative or even positive intrathoracic pressure.

Example 2

FIGS. 2A and 2B demonstrate the effects of breathing through tubes ofincreasingly narrower diameter. The subject breathed through each tubefor 1 minute and then normally for one minute. The data clearly showsthat as the diameter of the tube gets smaller, there are increasedswings in both the PAC and VIC due to increasingly wider swings inintrathoracic pressure. The PAC takes on its characteristic saw-toothpattern during respiration through the resistors.

Accordingly, in the context of a sleep study, a patient believed tosuffer from obstructive sleep apnea breathes through a series ofresistors during inspiration prior to going to sleep. The changes in thePAC and VIC can be recorded for several resistors. This information canbe stored in a proper storage medium. While the patient is sleeping, thedegree of inspiratory airway obstruction can be more accurately gaugedby calibrating the signal, i.e., comparing the changes in the PAC andVIC with those obtained during the patient breathing through resistorsbefore going to sleep. The resistors may configure such that they onlyresist either inspiratory air flow or expiratory air flow. This willfurther augment the patient's profile to facilitate differentiation ofthe type of obstruction or restriction a patient is suffering from andtherefore more accurate diagnosis. As stated above, knowledge of themaximal changes from photoplethysmograph “baseline” in the VIC andhaving baseline measurements taken when the patient is in remission canbe used to gauge the severity of an asthma attack or the degree ofairway obstruction during OSA. Of course, the device that processes thephotoplethysmographic signal can use any of a number of scales orsymbols to quantitate the degree of illness.

Example 3

In FIG. 3, there is shown a system 50 for obtaining and processing datafrom a patient for purposes of diagnosing sleep apnea, or otherrespiratory-related sleep disorders. The system comprises a computer 51that is configured to receive and process signals from lines 52 and 54,which are distally connected to one or more pulse oximeter probes (notshown) located on the patient. Those skilled in an will appreciate thatthe signals may be preprocessed to some degree by a separate signalprocessor and subsequently sent as one signal stream to the computer 51.Thus, the computer 51 is configured to receive signals from either lines52 or 54 or a combination of both. Typically, one of the lines willcarry power from the computer 51 to the pulse oximeter probe, while theother line carries signals back to the computer 51. The computer 51comprises a processing module 56 with program code module(s) and/orelectrical/circuitry components associated therewith to direct theprocessing of the signal stream from lines 52 and/or 54. The processingmodule 56 separates out the venous impedance component from the signalstream as described above. The processing module 56 also comprises aprogram code module(s) and/or electrical/circuitry components associatedtherewith to analyze the signal stream to determine inspiratory,expiratory, and/or air Obstruction events. In a preferred embodiment,the processing module 56, or a separate processing module, is directedto generate a report indicating the frequency, duration and/or severityof air obstruction events. Each event may be given a value based onpredetermined parameters. The computer can utilize the informationobtained from the procedure described in Example 3 above to moreaccurately gauge the severity and type of air obstruction event. Thisinformation provided by the computer will enable a physician todiagnosis whether the patient has a respiratory-related sleep disorder,as well as judge the severity of such disorder, which, in turn, willenable the physician to prescribe an appropriate treatment.

Furthermore, the computer 51 comprises a display 55 showing the signalproduced by the pulse oximeter probe as well as displaying informationregarding the processing and/or analysis of the data from the patient.Those skilled in the art will appreciate that the display, or othersuitable components, may be integral with, attached to or separate fromcomputer 51. The computer may also comprise a control panel with akeyboard, buttons, and/or touchpad to input commands or otherinformation. The computer may be a lightweight, portable computerapparatus that will allow the patient to conduct a sleep study at thecomfort of their home. The patient is provided with the portablecomputer box, probe(s) and probe lines, whereby the patient can engagethe probes to a central source site and conduct the testing herself.

FIG. 4 is a representation of a similar system where the components areseparated. A Those skilled in the art will readily appreciate that twoor more components of the system may be combined into a single housingunit or, alternatively, two or more components may be separate butconnected through appropriate wires, or wireless communication means.The system 60 comprises a signal processor 66 which is configured tosend/receive signals to/from lines 62, 64 which are connected to a pulseoximeter probe (not shown). The signal processor 66 comprises aprocessing module 68 configured to separate out the PAC and VICcontained in the signal stream received from the pulse oximeter probe.The PAC signal stream and/or the VIC signal stream is sent to a computer61 through line 63. The computer 61 comprises a processing module 69 toanalyze the PAC signal stream and/or VIC signal stream to monitorinspiratory and/or expiratory respiration events, or determine theoccurrence of an abnormal respiration event. Information generated fromthe signal process 66 and/or computer 61 may be sent to a display 65 vialines 67.

In the context of monitoring apnea, the FDA presently requires that anapnea monitor have at least 2 separate measures of the cessation ordecline in respiratory rate to insure that apnea or significanthypoventilation is detected. Many parameters have been used in anattempt to develop a reliable apnea monitor. This device must never havefalse negatives, since this result in the patient being apneic withoutan alarm from the device indicating so! False positives are less of aconcern, unless they are frequent enough to cause the user to disablethe alarms!

Potential parameters for apnea monitors include end-tidal CO₁, flowsensors, thermistors, pressure sensors and impedance monitoring at thechest. Pulse oximetry has been found to be an unreliable indicator ofapnea and hypoventilation because of excessive delays in detection of adecline in oxygen saturation (especially if the patient is onsupplemental oxygen) and delays due to signal processing.

Combinations of these parameters would meet the FDA requirement, but nocombination of 2 of the parameters has been shown to reliably diagnoseapnea without false negatives. Monitoring of the VIC, especially ifsensors were placed at more than one site to reduce the potential forinterference from motion artifact in combination with a traditionalparameter is likely to meet the FDA criteria. First, motion artifactsare significantly less at most central sites than on the fingers or toesand secondly the improved signal to noise ratio of the central signalswill make signal processing for determination of motion artifact easier.The combination of photoplethysmography, especially the processing ofthe VIC, in conjunction with capnography, temperature, flow or pressuresensing would likely meet the FDA criteria for an apnea/hypopneamonitor.

Example 4

Use of photoplethysmography may be employed as a surrogate for invasiveCVP measurements and/or volume status. Measurement can be made of apatient who is, for instance, in an ICU, cath lab or OR and has CVPcatheter in place. The airway maneuvers described above for Example 1can be performed and the changes correlated with the CVP measurementand/or the changes in CVP seen with the airway maneuvers. At a latertime, when the CVP catheter is removed, changes in the venous impedancecomponent can be correlated with the values obtained when the CVP was inplace. This should be a good indicator of the CVP and/or volume statusas long as there is no change in pulmonary function/status. It is wellknown in the art that CVP may be used as an index for a patient's volumestatus.

Accordingly, in another embodiment, the subject invention pertains to amethod of determining CVP without the need for a CVP catheter comprisingpositioning a CVP catheter in a first patient effective to produce CVPinformation; positioning on a central source site of said first patienta probe effective to generate a plethysmography signal stream;correlating plethysmography signal information from said probecontemporaneous to said CVP information to produce correlative CVPphotoplethysmography information; and determining CVP in said firstpatient or a second patient, without having a CVP catheter in place,wherein said determining employs said correlative CVPphotoplethysmography information. By extension, volume status of apatient may be determined through use of photoplethysmography probewithout the need for a CVP catheter. Through empirical studies arelationship between the venous impedance component and CVP isdetermined. As this relationship is established, the need for insertinga CVP catheter for purposes of obtaining correlative CVPphotoplethysmography information is diminished.

Accordingly, in a further embodiment, the subject invention pertains toa method of determining CVP and/or volume status of a patient comprisingpositioning on a central source site of a patient a probe effective togenerate photoplethysmography information; processing saidphotoplethysmography information to produce a VIC; and determining CVPand/or volume status through employing said VIC.

Example 5

FIG. 5 shows diagram of one method embodiment 500 for determining theoccurrence of an air obstruction event during sleep. The method 500comprises the step of obtaining photoplethysmography signals from acentral source site of a sleeping patient 505 and processing thephotoplethysmography signals obtained in step 505 so that the PAC andVIC signals are separated 510. Upon the PAC and VIC signals beingseparated, either of the signals, or both, are analyzed to determinewhether the patient has experienced any airway obstruction events 515.

Example 6

FIG. 6 shows a diagram of a method embodiment 600 for determining theoccurrence of an air obstruction event, including the magnitude of suchevent. The method comprises obtaining photoplethysmography signals froma central source site of a patient breathing through a series ofresistors 605. The signals obtained in 605 are processed to obtaincalibrations for inspiration and expiration events 607. This may involveseparating out the PAC and VIC and storing information such as magnitudeof the respective signals and correlating those with the resistor beingused. The resistors may include a series of tubes that sequentiallycomprise an ever constricted airway to an ultimately blocked airway. Toconduct a sleep study on a patient, photoplethysmography signals areObtained from a central source site of a sleeping patient 610. Thephotoplethysmography signals are processed to separate the PAC and VIC615. The component signal streams are then analyzed for the occurrenceof any abnormal respiratory event 620. This step involves the employmentof information obtained from steps 605 and 607 in order to determine thepresence of such event, or the severity of such event 625. The methodthen optionally involves generating a report that presents the patient'srespiration and the occurrence of abnormal respiration events 630.

Example 7

In a more specific embodiment as diagramed in FIG. 7, the inventionpertains to a method 700 of obtaining, processing and analyzingphotoplethysmography data for purposes of identifying abnormalrespiratory events during sleep. The method comprises collectingplethysmography signals from a central source site of a sleeping patient705. Peaks and, troughs of the photoplethysmography signals areidentified 710 Next, midpoints or minimum values between the peaks andtroughs identified in step 710 are identified. The interpolated lineconnecting these midpoints represents the venous impedance component.The PAC and VIC are separated 720, and then individually analyzed, orboth analyzed to determine occurrence of abnormal respiratory event 725.

Example 8

FIG. 8 represents a diagram of a method embodiment 800 for monitoringrespiration of a patient. In this method 800, photoplethysmographysignals are obtained from a central source site of a patient 805. Thephotoplethysmography signals obtained from step 805 are processed toseparate out the PAC and VIC 810. The VIC signal stream is then analyzedto monitor inspiration and expiration of the patient 815. Naturally, thesteps 805-815 are conducted in real time in order to properly monitorrespiration, which is typically carried out by a computer comprising aprocessing module directed by program code modules.

Example 9

In addition, the VIC and PAC can be used in combination to determineoptimal ventilator settings in patients requiting mechanicalventilation. Reference is made to U.S. Pat. No. 7,024,235. Knowledge ofintrathoracic pressure can be used to optimize various ventilatorsettings such as pressure support ventilation, mechanical ventilationparameters such as tidal volume, peak flow, and flow waveforms. Inaddition, the PPG could be used to estimate derivatives of intrathoracicpressure such as work of breathing and power of breathing. Changes inthe PPG also may indicate excessive positive end expiratory pressure(PEEP), allowing PEEP settings to-be optimized.

One embodiment pertains to a system that continuously determines theoptimal level of PEEP based on the PAC and VIC. The system can be closedloop or open loop where the clinician uses the information from the PPGto modify PEEP. In a closed-loop system, the ventilator automaticallyadjusts PEEP based on changes in the PAC and VIC without clinicianinput. In an open loop system, the ventilator or monitor would recommendchanges in PEEP to the clinician, keeping the clinician in control ofchanges.

When a patient is placed on a mechanical ventilator, PEEP is oftenapplied to improve oxygenation and prevent the collapse of vulnerablealveoli. Initially, the PEEP may be set at 5-10 cmH₂O and theconcentration of oxygen is increased above ambient to 30-40% (F₁O₂). Anarterial blood gas is obtained and if the patient is hypoxemic theclinician has two choices: improve oxygenation by increasing theconcentration of oxygen and/or increasing the level of PEEP. Each choicehas significant consequences. Oxygen concentration is usually kept below60% to prevent oxygen toxicity and/or collapse of alveoli due todenitrogenation (replacement of nitrogen in the alveolus with oxygen,which is absorbed resulting in alveolar collapse). While some cliniciansfavor increasing oxygen concentration over increasing PEEP, most try tokeep the F₁O₂at or below 40%. At this point improvement in oxygenationis usually attempted by further increases in PEEP. While increasing PEEPfrequently improves oxygenation, “over PEEP” can have seriousconsequences. PEEP increases intrathoracic pressure throughout therespiratory cycle and consequently can inhibit the return of blood tothe right side of the heart. This can result in a drop in ventricularfilling and consequently blood pressure which is recorded with anindwelling arterial catheter and/or noninvasive blood pressuremeasurements, in general this is a late finding and can be treated byreducing PEEP or by increasing intravascular volume with fluid infusionsto maintain ventricular filling and blood pressure (cardiac output).

Conventionally, the PEEP is titrated upwards based on arterial bloodgases and/or oxygen saturation measured with a pulse oximeter.Clinicians look for evidence of “over PEEP” by evaluating the arterialtracing, blood pressure, cardiac output (if measured) and thephotoplethysmograph. Unfortunately, many patients do not have arterialcatheters due to their complications. Likewise cardiac output is rarelymeasured due to frequent complications from CO catheyers. Also, thephotoplethysmograph is, according to standard protocols, processed andaveraged, so it rarely shows reliable changes in amplitude thatcorresponds to diminished cardiac output. Determining when a patient is“over PEEPed” without the need for blood pressure or other invasivemethods is a significant advantage over existing methods.

The inventors have discovered that this issue can be resolved bycontinuously evaluating the PAC and VIC. When a patient is “over PEEPed”the PAC falls, often dramatically, indicating diminished blood flow tothe head (and brain) since the increased PEEP (and therefore increasedintrathoracic pressure) is inhibiting venous return. Simultaneously, theVIC amplitude increases significantly since the patient is makingincreased respiratory effort (especially during exhalation). Thiscombination of findings can be used by the clinician to decide to (1)lower PEEP, (2) give the patient additional fluids, or (3) increase theF₁O₂. If the clinician is satisfied with the arterial blood oxygenationthen a closed-loop algorithm can be implemented to maintain the PAC andVIC amplitudes within a narrow range. The closed-loop would periodicallyevaluate the PAC and VIC and raise or lower the PEEP accordingly.Preliminary results in a small number of subjects indicates that theyoften tolerate increases in PEEP with little change in blood pressure orcardiac output until a “threshold” is reached, after which there is asignificant decline in these parameters. Continuous measurement of PACand VIC are early indicators for when the optimal PEEP is reached andwhere additional PEEP will be deleterious.

FIGS. 9A-9C. 10A-10C and 11A-11C show the effects of modulating PEEP onthe (A) plethysmograph, (B) PAC and (C) VIC. FIG. 9A representsplethysmography readings from a patient undergoing assisted ventilationwith a PEEP of 12 cm water. The black tracing is raw signal coming froman afar sensor. Gray tracing is a signal coming from a finger sensor.FIG. 9B represents the PAC signal and FIG. 9C represents the VIC signalfrom the alar sensor. FIGS. 10A-10C show readings from a patientundergoing assisted ventilation with a PEEP of 17 cm of water. Underhigher PEEP, the PAC decreases (i.e., the area under the curvedecreases, FIG. 10B) representing a decrease in arterial blood flow outof the chest. The amplitude of the VIC increases (FIG. 10C), whichrepresents increased thoracic pressure and more respiratory effort. FIG.11A shows plethysmography readings from the patient undergoing assistedventilation with a PEEP of 22 cm of water. The PAC decreases evenfurther (FIG. 11B), while the VIC amplitude increases further (FIG.11C). These figures demonstrate that the PAC and VIC modulate as PEEP isadjusted, and that PAC and VIC information may be used to determineintrathoracic pressure, respiratory effort, arterial blood flow andallow optimization of PEEP settings.

Accordingly, another embodiment pertains to a method of optimizing PEEPin a patient undergoing mechanical ventilation. The method comprisesmonitoring PAC and/or VIC and adjusting PEEP depending on the PAC and/orVIC information. Those skilled in the art will appreciate that optimalPEEP settings can be empirically determined based on observations of PACand/or VIC readings in a larger patient population.

Example 10

Similarly, evaluation of the PAC and more importantly the VIC can beused to “optimize” CPAP (continuous positive airway pressure) forpatients breathing spontaneously without mechanical ventilator supportor more importantly for patients on home CPAP therapy for OSA. While astarting CPAP level is determined during a formal sleep in a sleeplaboratory, the actual optimal CPAP may be different when the patient issent home due to a wide range of factors including sleeping position,depth of sleep, other temporary causes of airway Obstruction such asupper respiratory infections, etc. Thus, if the VIC could becontinuously monitored with an inconspicuous sensor, such as an alarprobe (the patient is already using a face mask or nasal prongs), theCPAP could be continuously adjusted using a closed-loop algorithm tomaintain the VIC in a “normal” range. Further, this approach can be usedin any patient who would benefit from optimization of the VIC includingCOPD patients.

Those skilled in the art will appreciate that more than one probe may beused in conjunction with many of the embodiments of the invention.Reference is made to U.S. Pat. No. 6,909,912. With respect to such citedpatent, those skilled in the art will appreciate that obtaining U.S.Pat. No. 6,909,912. With respect to such cited patent, those skilled inthe art will appreciate that obtaining plethysmography readings at acentral source site and peripheral site will provide additionalinformation that may be helpful in monitoring for respiratory disorders,or implementation in the embodiments taught, for example, in Examples 9and 10 described above.

The disclosures of the cited patent documents, publications andreferences are incorporated herein in their entirety to the extent notinconsistent with the teachings herein. It should be understood that theexamples and embodiments described herein are for illustrative purposesonly and that various modifications or changes in light thereof will besuggested to persons skilled in the art and are to be included withinthe spirit and purview of this application and the scope of the appendedclaims.

We claim:
 1. A method of monitoring air obstruction in an individual,comprising (a) obtaining at least one calibration photoplethysmography(PPG) signal stream from the individual while the individualspontaneously breathes through at least one resistor having a knownresistance; (b) using a processing device to determine changes in the atleast one calibration PPG signal stream in response to an increase inresistance to the individual's breathing; (c) obtaining a monitoring PPGsignal stream from the individual during spontaneous breathing; and (d)using the monitored PPG signal stream to determine a calibratedresistance value, and using the calibrated resistance value to determinea level of obstruction of the individual's breathing.
 2. The method ofclaim 1, wherein the at least one calibration PPG signal stream and themonitoring PPG signal stream are isolated pulsatile arterial component(PAC) signal streams.
 3. The method of claim 2, wherein exhalation PACsignals decrease as air obstruction in the individual increases.
 4. Themethod of claim 2, wherein inhalation PAC signals increase as airobstruction in the individual increases.
 5. The method of claim 1,wherein the at least one calibration PPG signal stream and themonitoring PPG signal stream are isolated venous impedance component(VIC) signal streams.
 6. The method of claim 5, wherein exhalation VICsignals increase as air obstruction in the individual increases.
 7. Themethod of claim 5, wherein inhalation VIC signals decrease as airobstruction in the individual increases.
 8. The method of claim 1,wherein the individual is determined to be partially or fully occludedif the monitored PPG signal stream corresponds to a calibratedresistance in a range of 20 to 40 cm H₂O/L/s.
 9. The method of claim 1,wherein at least one calibration PPG signal stream is obtained while theindividual takes a series of normal breaths followed by a series ofbreaths with resistors having different known levels of resistance. 10.The method of claim 1, wherein the at least one calibration PPG signalstream and the monitoring PPG signal stream are obtained from a centralsource site.
 11. The method of claim 1, wherein the processing device isa hand-held device that comprises a readout screen that displaysinformation regarding the level of obstruction in the individual. 12.The method of claim 1, wherein the level of obstruction of theindividual is used to monitor asthma in the individual.
 13. The methodof claim 1, wherein the resistors only resist inspiratory or expiratoryair flow.
 14. A respiratory monitoring device, comprising a processorthat receives at least one calibration photoplethysmography (PPG) signalstream from an individual while the individual breathes through at leastone resistor having a known resistance; determines changes in the atleast one calibration PPG signal stream in response to increases inresistance to the individual's breathing; and uses a monitored PPGsignal stream to determine a calibrated resistance value, and uses thecalibrated resistance value to determine a level of obstruction of theindividual's breathing.
 15. The respiratory monitoring device of claim14, wherein the at least one calibration PPG signal stream and themonitored PPG signal stream comprise an isolated PAC signal stream, anisolated VIC signal stream, or both.
 16. The respiratory monitoringdevice of claim 14, wherein the at least one calibration PPG signalstream and the monitoring PPG signal stream are obtained from a centralsource site.
 17. The respiratory monitoring device of claim 14, whereinthe device is a hand-held device that comprises a readout screen thatdisplays information regarding the level of obstruction in theindividual.